Management and Prevention of Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency
Patients with G6PD deficiency must strictly avoid specific oxidant medications—particularly dapsone, methylene blue, primaquine, and rasburicase—and should be educated to recognize early signs of hemolysis including dark urine, sudden fatigue, jaundice, and abdominal pain. 1
Risk Stratification by Genetic Variant
The severity of G6PD deficiency depends critically on the specific genetic variant:
- Mediterranean variant (G6PD-B⁻): Causes potentially life-threatening hemolysis and requires the most stringent precautions 1, 2
- African variant (GdA-): Results in milder, self-limited hemolysis that is typically less severe 1, 2
- The Mediterranean variant predominates in men from Mediterranean regions, India, and Southeast Asia, while the African variant affects 10-15% of Black individuals 1
Absolutely Contraindicated Medications
Seven medications are definitively contraindicated and must never be used 3:
- Dapsone: A potent oxidant causing methemoglobinemia and severe hemolysis 1
- Methylene blue (methylthioninium chloride): Triggers severe hemolytic anemia 1
- Primaquine: Contraindicated in severe deficiency; may only be considered in mild-to-moderate deficiency (>30% to <70% activity) at reduced dosing of 45 mg once weekly for 8 weeks with close hematological monitoring 1
- Tafenoquine: Contraindicated when G6PD activity is <70% 1
- Rasburicase: Absolutely contraindicated 3, 4
- Pegloticase: Should not be used until G6PD testing is performed 4
Both primaquine and tafenoquine are contraindicated during pregnancy regardless of G6PD status 1
Medications Requiring Caution
Moderate-Risk Medications
- NSAIDs (ibuprofen, diclofenac sodium): Present moderate hemolysis risk and require close monitoring 3, 2, 5
- Aspirin: Explicitly contraindicated as it overwhelms reduced antioxidant capacity 3
- Chloroquine/Hydroxychloroquine: Relatively safe in standard doses for most G6PD-deficient patients, and chloroquine may be used during pregnancy 1
Safe Antimalarials
- Artemisinin-based combination therapies (ACTs): Including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine can be used safely for malaria treatment 1
Safe Antibiotics
- Penicillins (including amoxicillin): Not contraindicated and can be used in normal therapeutic doses 3
Screening and Diagnosis
Pre-Treatment Screening
Screen all patients with Mediterranean, African, Indian, or Southeast Asian descent before starting oxidant drugs. 1, 3
- Qualitative screening is sufficient for initial assessment 1, 3
- Quantitative testing may be needed for borderline cases (30-70% of normal activity) to determine specific variant and predict severity 1, 3
Timing Considerations (Critical Pitfalls)
- Avoid testing during acute hemolytic crisis: G6PD levels are falsely elevated because young reticulocytes have higher enzyme activity 3, 2
- Avoid testing during or immediately post-transfusion: This gives falsely elevated results 3
- Repeat testing after 3 months if initial testing occurred during hemolysis 3
Advanced Testing
- Molecular genetic analysis can detect up to 100% of mutations and may be required when enzymatic testing is inconclusive, particularly in heterozygous females 3
Recognition of Acute Hemolytic Crisis
Classic Clinical Triad (24-72 hours post-exposure) 2, 5:
- Pallor (present in 100% of cases) 5
- Dark red/brown urine (hemoglobinuria) without RBCs on microscopy (present in ~90% of cases) 2, 5
- Jaundice (present in ~88% of cases) 5
Additional Symptoms 1, 4:
- Sudden fatigue
- Abdominal or back pain
- Anemia
Common Precipitating Factors
Based on a large Egyptian cohort study, the frequency of triggers is 5:
- Dietary triggers (83.4%): Fava beans (32.6%), falafel (19.4%), chickpeas (10.8%), broad beans (7.6%)
- Infections (12.4%): Pneumonia, tonsillitis, typhoid fever, hepatitis A, urinary tract infections
- Medications (4.2%): As listed above
Management of Acute Hemolytic Crisis
Immediate Supportive Care
- Provide aggressive intravenous hydration to maintain renal perfusion and reduce risk of hemoglobin-induced kidney injury 1
- Continuously monitor for acute kidney injury from hemoglobinuria 1
- Monitor hemoglobin levels closely, especially during acute crisis 3
Transfusion Threshold
- Consider transfusion if hemoglobin drops below 7-8 g/dL with symptoms 3
Laboratory Findings
- Normocytic normochromic anemia with reticulocytosis 5
- Heinz bodies on peripheral smear 5
- Elevated indirect bilirubin (>1.0 mg/dL when total bilirubin ≤5 mg/dL) 3
Chronic Management
Supplementation
- Folic acid 1 mg daily is recommended for all patients with G6PD deficiency 3
Patient Education
Educate all patients and families to: 1, 3
- Recognize early signs of hemolysis (dark urine, fatigue, pallor, jaundice, abdominal/back pain)
- Avoid all contraindicated medications and oxidant triggers
- Avoid fava beans and other high-risk foods
- Seek immediate medical attention when symptoms develop
- Inform all healthcare providers of their G6PD deficiency status before receiving any new medication
Preventive Measures
- Maintain a written list of contraindicated medications 1
- Screen for G6PD deficiency before starting any oxidant drug therapy 1
- Avoid exposure to known dietary triggers, particularly fava beans 5
- Treat infections promptly, as they are a major precipitant of hemolysis 5
Special Populations
Neonates
- Children of any age can develop hemolysis from contraindicated medications, and the same restrictions apply 1
- The highest prevalence of hemolytic crisis occurs in the 1-3 year age group (mean age of first presentation: 22.8 months) 5
- Mefloquine is not indicated for children <15 kg, and doxycycline is contraindicated in children <8 years 1